Oxygen makes up around 20 percent of the air around you. If it fell to 5 percent, you’d pass out after 3 minutes or so. Then, your brain would start to die. To fuel itself, this gas-guzzling organ requires a constant supply of sugar and oxygen—even when you’re not doing anything. Without the vital gas, ions flood across the barriers of neurons, causing internal havoc, and forcing them to self-destruct. “There’s probably more than a hundred things that will kill brain cells if you turn off the oxygen,” says Thomas Park, from the University of Illinois at Chicago.
Within minutes, you’d be dead. And hours after that, a naked mole-rat in the exact same conditions would be happily walking around—the picture of health. Imagine a disembodied index finger that’s been soaking in the bath for too long, and has teeth at the end. That’s a naked mole-rat. These weird rodents live in large underground colonies with nesting chambers the size of footballs. In these cramped subterranean quarters, oxygen levels often fall as low as 6 percent. And yet, these animals cope with this hypoxia.
Park knows this because he and his colleague Jane Reznick once put captive naked mole-rats into a chamber with just 5 percent oxygen—conditions that would kill mice in 15 minutes. “We were ready to pull them out at a moment’s notice if they started to look bad. And they looked fine,” Park says. “At five hours, we quit because I had to go home.”
Next, Park deprived the animals of all their oxygen. Under these conditions, no mouse can survive for more than a minute. But naked mole-rats? Although they lose consciousness after 30 seconds, and their heart rates crash after two minutes, and they stop breathing entirely after seven minutes, they can survive for a ridiculous 18 minutes. “We think they go into a state of suspended animation,” Park says. If they inhale some precious oxygen at the 18-minute mark, they spring back to life, with no sign of brain damage.
Some cold-blooded animals like carp, goldfish, and freshwater turtles spend months in frozen, oxygen-free lakes by lowering their body temperatures and shutting down their metabolism. But no warm-blooded mammal can match that feat, and none of them come close to the naked mole-rat’s 18-minute record.
With naked mole-rats, the unexpected is expected and the extraordinary is ordinary. They live in cooperative colonies like ants and bees, where a single queen suppresses the reproduction of her daughters, which act as her workers. They’re terrible at controlling their body temperature, and their sperm are misshapen and feeble. They’re exceptionally long-lived for rodents, with lifespans of up to 31 years. They feel no pain. They’re largely cancer-proof. And, as Park showed, they are absurdly tolerant to low oxygen levels.
Jaya Krishnan, a researcher at Imperial College who also studies hypoxia, suspects that mole-rats’ low body temperature—a tepid 30 degrees Celsius—may be responsible. Without having to heat themselves to the usual 37 degrees, they require less energy than a mouse or human. Indeed, when Park’s team repeated their experiments with naked mole-rats than had been warmed to 37 degrees, the rodents only lasted for 6 minutes. That’s less than 18, but still far better than other mammals. There must be another explanation.
To find it, the team looked at the chemicals that build up in the creature’s heart, brain, and other organs as the oxygen-free minutes tick by. One substance jumped out—a sugar called fructose, found in many plants. The mole-rats not only contained more of this sugar, but also all the molecular pumps and enzymes they need to import it into their cells and burn it for energy. And while these enzymes are typically found in the kidney alone, the mole-rats deploy them in their hearts and brains, too.
Most mammals, from humans to mice, use glucose as an energy source, burning it in the presence of oxygen. Burning fructose doesn’t require oxygen, but it’s also far less efficient, which is why we either store it, convert it into other sugars, or turn it into fat. But Park and Reznick showed that when oxygen disappears, naked mole-rats switch from burning glucose to burning fructose to release energy. They take the sugar from somewhere in their bodies, pump it into their cells, and so continue to survive.
Burning fructose comes at a cost. In the short-term, it produces lactic acid. In the long-term, other studies have suggested that burning fructose increases the risk of heart disease, diabetes, and cancer. “They obviously need other adaptations to make this work,” says Park.
For example, the mole-rats almost certainly get their fructose from their diet, but where do they store the sugar? When we humans eat a high-fructose diet, we convert the stuff into fat—which is why fructose has been linked to obesity and metabolic problems. “The next step is to identify how the mole-rats store fructose so they can use it directly without encountering the known issues of cancer and metabolic syndrome,” says Rochelle Buffenstein from Calico, who has worked with these animals before.
Park thinks this discovery might eventually be useful in protecting human health. Strokes, heart attacks, and other kinds of trauma are so lethal because they deprive the body—and the brain, in particular—of oxygen. Perhaps the naked mole-rat’s ability to shrug off a debilitating lack of oxygen might inspire new strategies for surviving these conditions. After all, we humans carry the same fructose-importing pumps and the same fructose-burning enzymes—we just don’t use them in the same way.
But for that reason, “translating the findings of this paper to a medical context might be challenging,” says Krishnan. That’s because naked mole-rats have a lot of proteins that import fructose into their tissues—a trait that humans do not share. Under normal conditions, it would be hard for us to send enough fructose to reach the brain or heart.
Along similar lines, other scientists are looking to the mole-rats’ bizarre biology for clues to killing pain and preventing cancer. Which raises the question: why exactly do these particular animals have such a cluster of weird traits? Why them, and not any other burrowing mammal like moles, badgers, or even other mole-rats?
“With the caveat that nobody really knows, my feeling is that it all relates to their ecology,” says Park. Millions of years ago, their ancestors migrated into the Horn of Africa—an arid region with very sparse resources. In these deserts, the naked mole-rats almost entirely feed on tubers—root vegetables about the size of a basketball. “If you find one, it’s payday for a long time, but they’re so dispersed that you need a large number of animals working together to find one,” says Park.
If they worked alone, as most burrowing mammals do, they simply wouldn’t find enough food. But a colony of 300 mole-rats can dig in a multitude of different directions, and collectively track down the scarce but bountiful tubers. That’s probably the origin of their ant-like social structures. And it explains a lot more. A large colony of underground animals would quickly use up all the available oxygen, so they needed to evolve ways of dealing with that. They started burning fructose, which produced lactic acid—maybe that’s why the mole-rats evolved an immunity to acid and pain. They also slowed down their metabolism, which might explain their very long life. And if you’re long-lived, you’ll need ways of avoiding cancer.
“It’s like we’re working with an animal from another planet,” says Park. “They’re so unusual because they’ve been evolving in this weird alien atmosphere for millions of years.”
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